Elucidation of the molecular mechanism and regulation of T-cell senescence

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02812
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Keio University
• Principal Investigator: SANO Motoaki 慶應義塾大学, 医学部(信濃町), 准教授 (30265798)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 炎症制御 / 線維化制御 / 心不全 / 慢性腎臓病 / 糖尿病 / 慢性炎症 / オステオポンチン / 免疫老化

Outline of Final Research Achievements

Accumulation of fat in visceral adipose tissue causes chronic inflammation due to infiltration of immune cells, mainly macrophages. We have found that osteopontin secreted by senescent T cells is involved in chronic inflammation in visceral adipose tissue. In the present study, we found that removal of senescent T cells by targeting PD-1 (Programmed cell death protein 1) improves glucose metabolism. This method would also remove activated T cells, which is not desirable. Regulation of transcriptional activity of osteopontin is important as a therapeutic target. We have been trying to clarify the mechanism of activation and regulation of the transcriptional activity of osteopontin, which is observed not only in visceral obesity but also in myocardial infarction and diabetic kidney disease.

Free Research Field

循環器、糖尿病内分泌代謝内科、免疫学、生化学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

肥満にともなうメタボリック症候群は、心筋梗塞、慢性腎臓病、心不全を引き起こし、健康長寿の妨げになる。これらの併存疾患の発症を予防するためには、肥満に伴う全身の炎症状態を軽減する必要がある。我々の研究は、オステオポンチンが心血管内分泌疾患発症を予測する、あるいは、治療効果を予測するバイオマーカーとして有用であることを明らかにしただけでなく、治療標的としても有望であることを明らかにした。